Manufacture of ureas, and substances of a like character of the naphthalene series



Patented Aug. 7, 1934 PATENT-7. OFFICE "MANUFACTURE on UBEASL, AND STANCES OF A LIKE CHARACTER 0F THE NAPHTHALENE seams George Malcolm Dyson, Cheadle Hulme, and

I A rnold" Renshavv, Manchester, England, as-

signors to'Parke Davis and Company; Detroit, Mich, a'corporation of Michigan v No Drawing. Application January 16, 1929, Serial No. 333,020. A 192 3.

Y Our invention relates to a new process for the manufacture of ureids of the naphthalene series including in this term; both ureas and thioureas.

We have found that by the action of the thionyl chlorideQphosphorus pentachloride, phosphorus triohloride and similar substances upon dicarboxylic aryl ureas," or dicarboxylic ar ylthioureas or their substitution products, anew series of aryl urea acid-halides is produced; we

have also found that similar substances may be produced by. the. action of thiori yl chloride, or phosphorus chlorides upon arylf-isocyanates or iso thiocyanates followed by treatment of the carbimi de or/thio-carbimide aryl acidyl halides so obtained with amino aryl carboxylic acids, amino carboxylic acid derivatives of quinoline, benzthiazole or the like followed by further treatment with thionyl chloride,

In carrying out the process of our invention we may-react diaryl ur ea acid,;halides, formed as above, with an amino-acenaphthene sulphonic acid or anamino naphthalene sulphonic acid or with their substituents. The diaryl ureaacid halides .may also be reacted with the products r-obtained by reducing the nitro compoundsfobtained by the action on l-amino-naphthalene sulphonic acids oi chlorides of nitro-aryl fatty acids and nitro' ary'l chlorides, nitro-aryl olefinic-carboxylicacid chlorides, nitro-aryl sulphuchlorides or theirisubstitution products, and in this way obtain symmetrical or unsymmetrical ureids which, are/of value as therapeutic agents or as intermediates for the production of colouring matters."

To. form the substituted amino-naphthalene sulphonic acids, with which 'our diaryl furea. acid halides can .be reacted toform the ureids of our invention; we may react up'ori'an' mm naphthalene sulphonic acid with a' nitroearyl" chloride, for example 2-nitr o-cinnamyl chloride (Berichte i6, 34, BeilsteinZ," 1414, 3rd editioriif (German- Patents 288',2 7 2 and 288,273), 4-nitroci nn'amyl chloride] (Berichte 1916, 49,2688) -,'1-nitr0-naphtha1ene 5- sulpho-chloride, l,5- nitro-naph thoyl chloride,- 2 nitrophenylacetyl chloride (Berichte 43,- 254p; 4-nitrophenyl-acetyl chloride, nitrobenzoyl chlo-' rides, nitroanisoyl chlorides, 'nitrotoluyl chlo rides, nitrobenzene 'sulpho chlorides, ChlOl'O-r nitrobenzoyl chlorides, .bromonitrobenzoyl chlo-.-:

3-nitrocinnamyl chloride .mentioned acid, 1naphthylamine-4,8-disulphonic acid, 1- "haphthylamine-4,6,8-tri-su1phonic acid, chloro- In Great Britain February 1','

17 Claims. (01. 260124) rides, iodonitro-benzoyl chlorides. The nitro groups in the reaction products of the above compounds with the amino-naphthalene sulphonic acids can be reduced to amino groups.

The productscanthen be termed amino arylido naphthalene sulphonic acids. "These bodies re-" acted with our diaryl urea acid halides produce the ureids of our invention.

Among the aminonaphthalene sulphonic acids which can be used in our process there may be 1,8-aminonaphthol-3 fi-disulphonic naphthylamine sulphonic acid, bro'moor 10610-- naphthylamine sulphonic acids, obtained by halogenating naphthylamine sulphonic acids by known .-methods or by, halogenating; the .acetyl-z naphthylamine s'ulphonic,v acids. 1 by known methods. and hydrolysing the products 1 alkoxyr. naphthylamine =5 sulphonic acids,- 1,5 -amino.-i;i

naphthol-fl sulphonic acid; .2,8-amino'naphtho1-,.

3,6..-'disulphonic acid. 1

H0: Y Nmand aminoacenaphthene .1 3 s ulphonic .j acid (Fleischer and Schranz, Ber..55, 3253 (1922'2;

G. T. Morgan and V. E. Yarsley, Journal of the Society of Chemical Industry, 44, 513T (1 925)), 4-aminoacenaphthene-3;5-disu1phonic acid" (G.

T. Morgan and V.- .E. Yarsley, Journal-of the Society ofChemical Industry, 44, 513T (1925)),

and i aminoacenaphthenetrisulphonic-acids, ob-

tainedbyiurther sulphonation of 4 -aminoacee, naphtheneTS-SulphOnic acid with oleum or, of 4 -nitroacenaphthene 5 sulpho ic acid with oleumand reduction of the N02 group.

To form the ureids of our invention we;-1 nayadvantageously use a urea or thiourea diaryl;

dicarboxylic acid as a starting material. I Exam-:, ples of these, bodies, which can be used our acid" separates and is removeda'nd dried.

process, are: symmetrical diphenylurea 3,3'-dicarboxylic acid, s-benzthiazolyl-phenyl urea 3,5 dicarboxylic acid, as-diphenyl urea 3,3 dicarboxylic acid, s-4-quino1yl phenyl urea 3,6 dicarboxylic acid:

ooH L -ooon S-oz-Z-IIlBthOXY phenyl-p-i-nitro phenyl urea 3:3 dicarboxylic acid:

7 I i CHa COOH OOH These urea or thiourea diaryl di'carboxylic acids may be represented by the following probable generic formula:

The dry diphenylurea 3,3 dicarboxylic acid is heated with thionyl chloride in excess until solu tion is complete. The excess of thionyl chloride is removed by distillation (with or without an inert liquid such as benzene) and the residual diphenyl-urea-3,3' dicarboxylic acid chloride (1 mol.) is stirred for several hours with an aqueous solution of the sodium salt of m-aminoparatoluyl naphthylamine-4,6,B-trisulphonic acid (0.9 mol.) with or without the addition of a mild alkali such as sodium carbonate, or sodium ace- 'tate, until the solution ceases to give a red coloration when treated with sodium nitrite, hydrochloric acid and resorcinol. The solution is fil tered from'tar, evaporated to dryness, preferably in vacuum, and extracted with methyl alcohol,

cipitated compound filtered off and dried.

The reactions taking place in the foregoing example may be illustrated as follows:

QCOONa-FCOCIHQCOOH NH I 1 v t R3 I NH: g V SO01 N vR: I 1 (Thiol yi =X NH H Chloride) I T Y -o00rrin which either R1 or Rarepresents hydrogen, v

NH NHT- ,-CO NH' soma +0 V +2 I If]:

the otherrepresenting a carboxyl substituted ary-l a I nucleus, R3 represents a carboxyl substituted CH1? aryl nucleus, X represents S, or O," andin which the aryl nuclei may be further substituted. These urea 'or thiourea di'aryl' dicarboxylic acids "are treated with thionyl chloride, phosphorus pentachloride or phosphorus trichloride to form the corresponding acid: chloride. The latter is then reacted with a primary arylamine or advanta geously with an amino-naphthalene 'sulphonic acid or an amino-acenaphthene sulphonic acid or an amino-arylido-naphthalene sulphonic acid to form the ureids of our invention.

The finished products may .be purified in any suitable manner, as, for instance, by solution in glacial acetic acid, or any other suitable solvent, and precipitation of the substance from solution by acetone, ether or other suitable precipitant.

As an exampleof this synthetic process the following manner of preparing a urea compound is citd:'

Exdmple.-m-aminobenzoic acid is dissolve in a dilute aqueous solution oi caustic soda andphosgene gas passed into the solution so obtained which may be artificially cooled; or, alternatively, the'solution of sodium ni-aminobenzoate is treated with a solution of phosgene in'an inert solvent such as tetrachlorethane or toluene; or, alternatively, the m-aminobenzoic acid may be dissolved in a mixture of non-aqueous solvents of which pyridine forms acomponent part,-and treated with pho sgene' alone or in solution. In each case, the compound diphenyl urea- 3z3f-dicarboxylic' 7 som OaNa I The process and reactions with are similar.

What we claim and desire to secure by Letters] Patent is:--

the thioureas l. The manufacture of a symmetrical urea derivative by dissolving m-aminobenzoic acid in a dilute aqueous solution of causticfsoda, passing phosgene gas intothe solution, heating the dry diphenyl-urea-B,3'dicarboxylic acid obtained. with thionylchloride in excess, removing the excess of thionyl chloride, stirring the residual diphenyl-urea-3,3-dicarboxylic: acid chloride with an 'aqueoussolution-zof, the sodium salt of m-' aminotoluyl-' naphthylamine 4,6,8 trisulphonic' .1 acid, purifying, and extracting with methyl al-.

'acid' chloride from a-compoun'd having'the "coholand separating the urea derivative by precipitation in absolute ethyl alcohol.

2. In the manufacture of open ring ureids, the process which comprises forming a diaryl 5 urea acid chlorides from a compound having the general formula:

NH Ri in which either R1 or R2 represents hydrogen, the other representing a monO-carboxyl substituted phenyl nucleus, R3 represents a monocarboxyl substituted phenyl nucleus, X represents S or O, and reacting said diaryl urea acid chloride with a compound selected from a group consisting of amino-naphthalene sulphonic acids, amino-arylido-naphthalene sulphonic acids and amino-acenaphthene sulphonic acids.

3. In the manufacture of open ring ureids, the

process which comprises forming a diaryl urea acid chloride from a compound having the gen- L eral formula:

in which either R1 or R2 represents hydrogen, the other representing a monocarboxyl substituted phenyl nucleus, R3 represents a monocarboxyl substituted phenyl nucleus, and reacting said diaryl urea acid chloride with a compound selected from a group consisting of amino-naphthalene sulphonic acids, amino-arylido-naphthalene sulphonic acids and aminoacenaphthene sulphonic acids. 4. In the manufacture of open ring ureids, the process which comprises forming a diaryl urea acid chloride from a compound having the general formula:

Ilia

NHR1

in which either R1 or R2 represents hydrogen, the other representing a monocarboxyl substituted phenyl nucleus, R3 represents a monocarboxyl substituted phenyl nucleus, X represents S or O, and reacting said diaryl urea acid chloride with an amino-arylido-naphthalene sulphonic acid.

5. In the manufacture of open ring ureids, the process which comprises forming a diaryl urea and acid chlorid from a compound having the general formula:

R: I l-R2 process which comprises forming a diaryl urea NEG-R1 general formula:

-NH-IR1 I IHR;

in which either R1 or R2 represents hydrogen, the other representing a mono carboxyl substituted phenyl nucleus, R3 represents a mono carboxyl substituted'phenyl nucleus, X represents S or O, and reacting said diaryl urea. acid chloride with a primary aryl amine.

'7. In the manufacture of open ring ureids, the step which consists in reacting with ,thionyl chloride upon diphenyl-dicarboxyl-ureas.

8. The manufacture of open ring ureids bya process which comprises first converting a dicarboxylic aryl urea into the corresponding acid chloride and then reacting such acid chloride with a primary aryl amine in which the aryl is one of the group consisting of acenaphthene and naphthalene.

9. The process of preparing complex ureas which comprises converting a dicarboxylic aryl urea into the corresponding di-acyl halide and then reacting such acyl halide with a primary aryl amine.

10. The process of preparing urea polyamides which comprises converting a dicarboxyl phenyl urea into the corresponding di-acyl halide and then reacting such acyl halide with an amino derivative of an amide to yield a urea polyamide.

11. A new process for the manufacture of complex urea derivatives involving the condensation of dicarboxy urea derivatives of the type in which X represents sulphur or oxygen, R represents hydrogen or alkyl, and R1 and R2 represent aryl nuclei, with aryl amines of the class consisting of amino-acenaphthene sulphonic acids and aminonaphthalene sulphonic acids to yield urea amides.

12. A new process for the manufacture of complex urea derivatives involving the condensation of dicarboxy urea derivatives of the type in which R represents hydrogen or alkyl, and R1 and R2 represent aryl nuclei, with aryl amines of the class consisting of amino-acenaphthene sulphonic acids and aminonaphthalene sulphonic acids to yield urea amides.

13. A new process for the manufacture of complex urea derivatives involving the condensation of dicarboxy urea derivatives with compounds of the type where R3 and R4 represent nuclei of the class consisting of phenyl andnaphthyl nuclei and y is not more than 3.

pound of the class consisting of a urea diaryl dicarboxylic acid and a thiourea diaryl dicarboxylic acid into the corresponding di-acyl halide and reacting said halide with an aryl amine.

15, The process comprising converting a compound of the class consisting of a urea diaryl dicarboxylic acid and a 'thiourea diaryl dicarboxylic acid into the corresponding di-acyl halide and reacting said halide with a compound of the class consisting ofjaminonaphthalene sulphonic acids and the salts thereof.

16. The process of preparing ureids of the naphthalene series comprising reacting a diaryl urea di-acid halide with an aminonaphthalene sulphonic acid. l

17. ;'Ihe process comprising converting acompound having the formula p HN-AnCO-Hal HN-ArzC Q-Hal with a compound having the formula NHz-AR3 thereby obtaining a compound having the formula H N-An0 ONH-Ara HN-ArzC O -NH Ara Where X 15 0 or S, An, Am and Ara are aromatic nuclei and Hal is halogen.

GEORGE MALCOLM DYSON. ARNOLD RENSI-IAW. 

